Emerging drugs of abuse — what doctors should know

7 classes of ‘synthetic designer drugs’ are featured in the Disease-A-Month journal

By Michael Nelson, MD; Sean Bryant, MD; and Steve Aks, DO Posted on 1 April 2014

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Introduction

Emerging drugs of abuse are a major concern for public health as well as law enforcement. The 2013 National Drug Threat Assessment Summary, issued by the US Drug Enforcement Administration (DEA), addresses the abuse of synthetic designer drugs and their increasing availability. The document points out that there are seven classes of synthetic designer drugs: cannabinoids, phenethylamines, phencyclidines or arylcyclohexamines, tryptamines, piperazines, pipradrols or N-Ring systems, and tropane alkaloids.

A new review article in the Disease-A-Month journal explores these emerging drugs in detail. The authors – Michael Nelson, MD, MS; Sean Bryant, MD; and Steve Aks, DO – address the specifics of clinical pharmacology, clinical manifestations, lab testing and imaging as well as treatment for the effects of these drugs. They provide a road map for family practitioners, generalists, and internists as well as clinical pharmacists, emergency physicians and medical toxicologists; any of whom may be confronted with patients who have used and abused these drugs.

The authors emphasize the challenge faced by practitioners to keep current regarding the ever-changing landscape of new drugs available on the Internet and elsewhere. Perhaps the most sobering aspect of the interesting and alarming public health threat is the fact that virtually none of this information is included in core curricula for medical schools or residency training programs. With their article, they aim to fill a critical informational void for trainees and practitioners alike.

This is a summary of their article. Elsevier has made the full article – including information on treatment regimens – freely available here.

Emerging drugs of abuse

Keeping up with emerging drugs of abuse will always be a challenge for physicians. As law enforcement agencies classify certain drugs as illegal, "street pharmacists" rapidly adapt and develop new congeners of old drugs for distribution and use.

Many of these drugs are marketed as "legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has led to a multitude of emergency department visits with severe complications including deaths worldwide.

Despite recent media attention, many of the newer drugs of abuse are still largely unknown by healthcare providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown.

It is essential that physicians have a solid foundation in the general classes of drugs of abuse.

Poison Centers along with local public health officials should be important sources of current information. Internet sites, social media, and search engines can be additional tools to stay on top of drug of abuse trends.

Following is a summary of our article for Disease-A-Month.[divider]

Synthetic Cannabinoids

Cannabis is one of the most widely used illicit substances worldwide and in the United States. In the last decade, synthetic cannabinoids (SC) gained popularity as a legal alternative to achieve euphoric effects similar to cannabis.

These products were sold at "head shops," convenience stores, and over the Internet as herbal incense or air fresheners and were marketed as "not for human consumption." The most common street names for SC are "K2" and "Spice." They did not fall under initial legal regulations from the US Federal Controlled Substances Act due to their structural dissimilarity to D9-tetrahydrocannabinol (D9-THC).

Additionally, multiple other biologic herbs besides SC are contained in these products. Packaging notoriously contains little information regarding the chemical composition of the plant products and no standard exists for the ingredients or concentrations. SCs are typically sold in metal foil sachets as a mixture of dried vegetable matter with the SC substance sprayed onto the herbal mixture.

Clinical effects

A wide variety of clinical effects have been reported with SC use from very mild symptoms to severe sympathomimetic-like effects and seizures. Also, due to variability of SC concentration and substances, recreational use can result in accidental overdose. The most common reported findings to poison centers include tachycardia, agitation, vomiting, drowsiness, confusion, hallucinations, hypertension, dizziness and chest pain.[divider]

Synthetic Cathinones (Bath Salts)

Synthetic cathinones, commonly sold as "bath salts," have recently emerged as a popular drug of abuse. They comprise a broad group of compounds with amphetamine-like effects go by a wide variety of common street names.

Their use has increased over the past decade as they were marketed as "legal highs" similar to synthetic cannibis and "not for human consumption" to avoid legal and regulatory oversight. They are sold at "head shops" and on the Internet similar to SC.

Cathinone occurs naturally and is found in the leaves of the khat plant. Khat leaves contain phenylalkylamine compounds (cathinone, cathine, and norephedrine) related structurally to amphetamine and noradrenaline and produce stimulant effects. Cathinone, however, appears to be the main constituent responsible for the amphetamine-like euphoria.

Synthetic cathinones are derivatives of cathinone with various chemical alterations effecting pharmacokinetics and pharmacodynamics.

Other Phenethylamines (2C drugs)

The basic phenethylamine chemical structure is shared among catecholamines, amphetamines, synthetic cathinones, and many other drugs. Another class of synthetic phenethylamines abused for recreational highs are the "2C" class of drugs, which relates to the 2 carbons between the benzene ring and the terminal amine group. They include MDMA (3,4-methylenedioxymethamphetamine), commonly known as "Ecstasy" and "Molly."

Individuals who seek Ecstasy at "dance raves" and music festivals may inadvertently be exposed to 2C drugs as contaminants or MDMA substitutes.

These substances, which generally come in tablet or powder form, can be purchased on the Internet and can be listed as "research chemicals." As with SC and synthetic cathinones, 2C users tend to be younger males and may have a history of polydrug use.

Many 2C substances are listed as Schedule I substances. Newer phenethylamine compounds, however, are continuously being designed and introduced to divert existing legislation and regulatory oversight. This produces a challenge to the treating physician in terms of being aware of new street names for these drugs.

Piperazines

Piperazine recreational drugs are fully synthetic substances and do not occur naturally. They were initially developed as anti-helminthic drugs (to treat parasitic worms) but later studied as anti-depressants.

Two main groups of piperazines are used recreationally: benzylpiperazines and phenylpiperazines. Piperazines may be found as constituents or substitutes in pills sold as Ecstasy or amphetamines. They can also come as mixtures of more than one piperazine (such as BZP/TFMPP) or in combination with other drugs of abuse. Piperazines are some of the most common active substances found in Internet purchased drugs, and typical users tend to be young males.

Clinical effects

Symptoms commonly experienced by users include insomnia, anxiety, headaches, nausea, tremors, shakiness, diaphoresis, dizziness, palpitations, shortness of breath, confusion, hallucinations and paranoia. Other potential serious effects can include seizures, QT interval prolongation, and hyponatremia. Due to the serotonergic effects of piperazines, serotonin syndrome is a risk especially if combined with other serotonergic agents. Additional life-threatening complications of BZP use include status epilepticus, hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, and renal failure.[divider]

Tryptamines

Tryptamines – which have a hallucinogenic effect – can be naturally occurring or synthetic. Naturally occurring tryptamines are derived from tryptophan and include serotonin, melatonin, psilocybin/psilocin and bufotenin. Synthetic tryptamines have structural similarity to serotonin and are abused for their hallucinogenic effects.

Like many other novel psychoactive substances, simple chemical substitutions to the base tryptamine structure allow for development of many new substances.

Routes of administration include insufflation, intravenous injection, intramuscular injection, oral, rectal, or vaporization depending on the substance and user.

Clinical effects

Tryptamines mainly cause hallucinogenic effects but also have stimulatory effects. Patients may also have tachycardia, hypertension and mydriasis. Agitation, psychosis, and excited delirium can occur with rhabdomyolysis and renal failure.[divider]

Kratom

Originating from a Southeast Asian tree (Mitragyna speciosa Korth), Kratom was traditionally used as early as the late 1800s by manual laborers from Thailand and Malaysia for the purposes of euphoria, stimulation, euphoria, analgesia, and opium withdrawal. Other "benefits" of Kratom include antipyretic, antihypertensive, anti-inflammatory, antidiarrheal, hypoglycemic, increased circulatory, and extended sexual prowess effects.

Currently, Kratom is readily available for purchase on the Internet and has notoriously gained popularity in its use and abuse.

Kratom is most commonly used for the hallucinogenic effects, but may also be used less commonly for management of opioid withdrawal. Mitragynine is merely one of over two dozen alkaloids within the plant, and is believed to be the one responsible for opioid-like effects encountered when higher doses are taken.

The drug is frequently smoked, but it can be ingested after being brewed into a tea.

Clinical effects

The most likely patient one would care for in the emergency department is the one presenting with either opioid effects or withdrawal. Since this agent is utilized for opioid withdrawal, and mitragynine has been describe to have a potency greater than 10 times that of morphine, Kratom withdrawal, too, is a possibility. It is indistinguishable from opioid withdrawal, with symptoms of yawning, rhinorrhea, diarrhea and irritability. [divider]

Salvia

While there are hundreds of species of Salvia, S.divinorum is the one most relevant to the emergency physician. A member of the mint family, Salvia is native to Mexico and has historically been used during religious ceremonies. The hallucinogenic properties after smoking it, ingesting a tea, or chewing the leaves of the plant are attributed to salvinorin A. Slang terms used for Salvia include magic mint, mystic sage and Sally D. Head shops or the Internet are a source of pre-packaged crushed leaves.

The hallucinogenic etiology of salvia differs from many other hallucinogens. Salvia stimulates kappa opioid receptors and is noted to result in perceptual distortions, pseudo-hallucinations, and an altered sense of self and environment. Chewing and allowing buccal absorption will result in these effects, but oral ingestion will not.

Classically, Salvia is smoked with deep inhalation with valsalva similar to smoking marijuana. The effects are rapid in onset (30 seconds to 10 minutes depending on route of ingestion) and quickly dissipate within a half hour. This brief and intense experience seems to be exaggerated in younger adults and adolescents, and many report visual distortions of body image, out of body experiences and hearing colors.

Clinical effects

The majority of people who use Salvia will not seek treatment at a healthcare facility. The most common symptoms include confusion, disorientation, hallucinations, giddiness or dizziness, and a flushed sensation. [divider]

Mushrooms

Magic "shrooms" refer to the class of mushrooms that contain the hallucinogenic chemical psilocybin, which is subsequently metabolized to psilocin. Because these compounds resemble serotonin, the subsequent clinical effects are much like LSD. Most of the time, these mushrooms are ingested and result in hallucinations, illusions, and ataxia within one hour.

Clinical effects

Symptoms include severe nausea, vomiting, diaphoresis, tachycardia, hyperthermia, and rarely seizures. Classically, patients presenting to the emergency department might be from a concert setting where they ingested mushrooms and experienced a "bad trip," or a college setting where recreational use is common.[divider]

Hawaiian Baby Woodrose (Argyreia nervosa)

Lysergamide (LSA) originating in plants may be abused as a hallucinogen as it is chemically similar to synthetic lysergamide or LSD (d-lysergic acid diethylamide). The seeds of the Woodrose (Argyreia nervosa) are eaten or consumed from an extract after being soaked in water. A commonly ingested dose is 5-10 seeds, which may yield a dose of 2-5 mg of LSA sufficient to result in hallucinations for a duration of 4 to 6 hours.

Head shops and Internet distribution account for the largest available market of seeds throughout Europe and the United States.

Clinical effects

Characteristic symptoms following use are typical of other hallucinogens; however, the effects may be differentiated from the anticipated LSD-like experience. While increased insight and positive emotional states (e.g., euphoria, happiness, delight, altered perceptions of colors and textures, mood elevations) may occur after exposure, negative effects may include tachycardia, hypertension, nausea, vertigo, mydriasis, anxiety, sedation and a sense of derealization.

In recreational users, feelings of loneliness, depression, and suicidal thoughts have also been reported.

Treatment

Often, patients presenting under the influence of a drug or substance abused for recreational purposes have an altered sensorium and are unable to provide a robust history surrounding the ingestion. Ideally, knowing the time, route and intent of use will assist in ultimate disposition.

Many of the current emerging drugs of abuse result in psychoactive and sympathomimetic effects with excited delirium.

Most of these drugs have no specific antidote, and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct.

Read the full article

Disease-A-Month

Disease-A-Month, published by Elsevier, is a journal for primary care physicians. Each issue presents an in-depth review of a single topic, including pathophysiology, clinical features of the disease or condition, diagnostic techniques, therapeutic approaches and prognosis. For more about the journal and a sample issue, visit the journal website.

Dr. Michael I. Greenberg, a member of the Disease-A-Month Editorial Board, specializes in medical, occupational and environmental toxicology. He has served as a clinical consultant for the Philadelphia Poison Control Center since 1994. He served as a medical officer with the US Marine Corps Reserve while in the US Naval Reserve from 1985 to 1995, and served on active duty during Operation Desert Storm. At the Drexel University College of Medicine, he is Program Director of Medical Toxicology; Chief of the Division of Medical Toxicology; and Professor of Emergency Medicine.